Morphological changes of isolated rat pancreatic islets: a structural, ultrastructural and morphometric study

Improved techniques for pancreatic islet extraction can yield a reasonable number of transplantable cells. However, the isolation and purification process may damage the islets and impair their physiological functions. The aim of this study was to determine the effect of the isolation procedure on the structure of isolated islets and to correlate this with their functionality. Islets were isolated from rat pancreata and purified by Eurocollins-Ficoll discontinuous density gradient processing, and then processed for light microscopy, and scanning and transmission electron microscopy. Morphometric analysis was also performed. Islet functionality was determined by reversal of streptozotocin-induced diabetes and the intraperitoneal glucose tolerance test in a syngeneic rat model of pancreatic islet transplantation. Fragments of variable size and shape comprised a relatively large proportion (26%) of the isolated endocrine tissue. Isolated islets showed slight alterations of cell ultrastructure. Major damage (including breakage of the plasma membrane) and loss of cells were observed in the peripheral cells of the isolated islets. An equal mass of islet equivalent (IEq, islets with an average diameter of 150 µm), but with a different islet equivalent/islet number ratio, was transplanted in diabetic animals. When larger and more complete islets were transplanted (higher ratio), better function of the graft was observed by reversal of hyperglycaemia and response to the glucose tolerance test as compared with the functionality and response of smaller (fragmented) islets transplanted (lower ratio). Digestion, trauma and hypoxia during isolation are responsible for qualitative and quantitative changes of isolated islets. Alterations in normal secretory function after the transplant were related to lower islet equivalent/islet number ratio. The incomplete integrity of the islets may explain the failure of the fine glycaemic metabolic regulation

Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility.

International audienceThe World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa